Clinical evaluation, research, and treatment of patients with manic-depressive illness, schizoaffective disorders, and anxiety disorders are the primary goals of the Section. Double-blind, placebo-controlled clinical trials are employed to evaluate routinely used and novel agents for the treatment of these disorders. Anticonvulsants such as carbamazepine have been demonstrated to be clinically effective in the acute and prophylactic treatment of manic-depressive illness. We have identified possible clinical and biochemical markers of response to lithium versus carbamazepine and other agents. For example, antimanic responders to carbamazepine appear to be more severely ill, more dysphoric, and more rapidly cycling than non-responders. In attempting to elucidate possible mechanisms of action, we have found that noradrenergic and "peripheral-type" benzodiazepine mechanisms may be important to the anticonvulsant if not the psychotropic effects of carbamazepine. Other neurotransmitter, modulator, and peptide substances are being studied which may account for carbamazepine's positive effects on mood and behavior. The Section also seeks to identify regional alterations in brain electrophysiological and metabolic activity that are related to changes in behavior and cognition in affective illness. A clinical probe of limbic system excitability utilizing a novel provocative agent, procaine, is also being employed. Procaine selectively increases fast activity over the temporal lobe in association with a variety of behavioral and cognitive alterations and secretion of cortisol, ACTH, and prolactin. Animal models of electrophysiological kindling, stimulant-induced behavioral sensitization, and unavoidable stress or "learned helplessness" are studied by the Section. These models may help provide new clinical and biochemical insights, as well as suggesting possible basic neurophysiological and biochemical mechanisms that might underlie these long-term changes in behavior.